The present invention relates to a device for non-invasive depth-selective detection and characterization of surface phenomena in organic and biological systems such as tissues by surface measurement of the electrical impedance of said material with said device as well as a method for said surface characterization.
Electrical impedance is a very sensitive indicator of minute changes in organic and biological material and especially tissues such as mucous membranes, skin and integuments of organs, including changes due to irritation caused by different reactions, and scientists all over the world have worked hard to find a convenient way to measure variations and alterations in different kinds of organic and biological material to be able to establish the occurrence of such alterations which are due to different states, characteristic of irritations from e.g. diseases.
Much of the fundamental knowledge within the current area stems from the field of electrochemistry. Potentiostats have for a long time been in use for studies of e.g. corrosion, and AC (alternating current) methods have gradually evolved and are well documented, cf. Claude Gabrielli: Identification of electrochemical processes by frequency response analysis. Solartron Instruments technical report number 004/83, 1984 and F. B. Growcock: What's impedance spectroscopy. Chemtech, September 1989, pp 564-572.
Excellent tools for work in this field are available, e.g. the 1286 Electrochemical Interface, Solartron Instruments, UK and the Model 378 Electrochemical Impedance Systems, EG&G Princeton Applied Research, N.J., U.S.A.
Characteristic features of these systems are that they are intended for use with specimens mounted in appropriate electrochemical cells.
It is well known that certain parameters in living tissues are reflected by electrical impedance of said tissues: U.S. Pat. No. 4,038,975 (Aug. 2, 1977) to Vrana et al. relates to an electrically instrumented method of diagnosing the presence of a neoplast in mucuos membrane samples wherein the electrical impedance of the sample has resistive and capacitive components and wherein the relative values of said components are indicative of the presence or absence of said neoplast by associating the sample with the terminals of a series circuit including in succession a grounded, amplitude-modulated high-frequency generator and first and second equal-valued resistors wherein the impedance of the generator and the resistance of both resistors are low relative to the impedance of the sample. Said association being made by connecting a test spot on the sample to the terminal of the second resistor remote from the junction of the first and second resistors and by connecting the bulk of the sample to the grounded terminal of the generator, simultaneously measuring the amplitudes of the potentials of the test spot and of the junction of the first and second resistors with respect to a reference value established at the junction of the generator and the first resistor, and computing from the measured values and from the reference value the resistive and capacitive portions of the impedance of the test spot.
By EP 0 315 854 (Appln. No. 88118083.0) to Honna is previously known a method and a system for measuring moisture content in skin by passing "weak" low frequency electric current through the keratinous layer between two electrodes abutted upon the skin, amplifying the electric voltage appearing on the layer, rectifying and taking out signals of the amplified output, and measuring the amplitude of the signal, which is characterized in that the voltage appearing on the keratinous layer is the voltage appearing between either one of said two electrodes whichever is closer to another electrode which is abutted upon said skin at a location outside said two electrodes.
The system comprises a measuring electrode structure of triple concentric circles including a central electrode, an intermediate electrode and an outer electrode all of which can be abutted on the skin, a generator which uses one of said electrodes as a common electrode and supplies low frequency signal between this common electrode and another of said three electrodes; an amplifier which converts the resulting current into a voltage appearing between said common electrode and yet another of said three electrodes, and a means to display the output voltage of the amplifier which is characterized in that a circuit means is provided for switching between a first circuit using said intermediate electrode as common electrode and a second circuit which uses the outer electrode as a common electrode.
Further prior art is disclosed in e.g. Yamamoto, T. & Yamamoto, Y.: Analysis for the change of skin impedance. Med. & Biol. Eng. & Comp., 1977, 15, 219-227; Salter, D. C.: Quantifying skin disease and healing in vivo using electrical impedance measurements. In: Non-invasive physiological measurements, Vol 1, 1979, Peter Rolfe ed., pp 21-64; Leveque, J. L. & De Rigal, J.: Impedance methods for studying skin moisturization. J. Soc. Cosmet. Chem., 1983, 34, 419-428; and Morkrid, L. & Qiao, Z.-G.: Continuous estimation of parameters in skin electrical admittance from simultaneous measurements at two different frequencies. Med. & Biol. Eng. & Comp., 1988, 26, 633-640.
Characteristic of existing technology in this field is that either:
a) a biopsy would have to be excised in order to well define the actual tissue under test, i.e. not suitable for in vivo measurements; or PA1 b) electrodes are applied to the skin at separate sites, directing the electric test current right through the skin and regarding the inner part of the skin and deeper lying tissue as an almost ideal short circuit between the contact sites, i.e. no discrimination between the layers of the rather complicated anatomy of the skin.
There are devices for measuring the water content in the outermost layers of the skin (such as the Corneometer CM820PC, Courage+Khazaka Electronic GmbH, FRG) using interdigitated electrode patterns. A device called DPM9003 from NOVA Technology Corporation, Mass., U.S.A. employs a simple coaxial electrode. These devices have no means for controlling the measurement depth except for the limitations set by physical size. Indeed, they are applications of the well known principle of moisture measurement using fringing fields (Giles: Electronic sensing devices, Newnes, London, 1966/68, pp 80-81).
A device for measuring conductance of the fluids in mucous membranes of the airways has been published (Fouke, J. M. et al: Sensor for measuring surface fluid conductivity in vivo. IEEE Trans. Biomed. Eng., 1988, Vol 35, No 10, pp 877-881). This paper shows, backwards, the problem encountered while measuring on wet surfaces without a control electrode to enforce depth penetration.
It is possible to use Applied Potential Tomography/Electrical Impedance Tomography to obtain tomographic images of e.g. thorax or gastric regions, employing a large number of electrodes around the body and computing with reconstruction algorithms an image representing changes of conductivity in the body (Seagar, A. D. & Brown, B. H.: Limitations in hardware design in impedance imaging. Clin. Phys. Physiol. Meas., 1987, Vol. 8, Suppl. A, 85-90).
According to the present invention depth selectivity is achieved by controlling the extension of the electric field in the vicinity of the measuring electrodes by means of a control electrode between the measuring electrodes, the control electrode being actively driven with the same frequency as the measuring electrodes to a signal level, taken from one of the measuring electrodes but also multiplied by a complex number, in which the real and imaginary parts are optimized for each application depending upon the desired depth penetration. The function of the controlling field is analogous to that of a field effect transistor, well known from solid state physics. In biological tissue or "wet state", conduction mechanisms are complicated involving a number of ions, polarization effects, charged or polarizable organelles, etc. However, no reconstruction algorithms are needed to achieve depth selectivity, although consecutive measurements at different depths must be recorded in order to obtain a profile.
The principle is basically frequency independent, and works from DC to several MHz. Simple impedance measurements at one or a few frequencies, as well as impedance spectroscopy in this range can thus be done depth selective on e.g. skin.
In mucous membranes the fluid on the surface would normally short circuit measuring electrodes placed on the same surface; however, by use of the control electrode the test current is forced down into the mucous membrane rather than taking the shortest way and local definition of the actual tissue under test is thus achieved. These advantages are directly applicable while measuring impedance as an indicator of irritation during tests of irritants on skin and oral mucous membranes. It was also possible to measure impedance on kidneys while at the same time measuring the blood pressure within the kidney in the main artery, and it was found that impedance descriptive parameters correlated well with blood pressure. This opens the possibility to measure pressure, as well as microcirculation non-invasively in many organs during surgery by applying a probe to the surface of the organ. Another application is the measuring of pressure in the eye (diagnosis of glaucoma).